Precursor B cells from mouse spleen and bone marrow can be induced in vitro to express the surface markers Ig, Ia, CR and Pc.1. Our evidence points to the existence of four different populations each acquiring when induced, one of the markers. We postulate at least five compartments in the B lineage and a sequential development from Ig- to Ig ion Ia- to Ig ion Ia ion CR- to Ig ion Ia ion CR ion Pc.1- to Ig ion Ia ion (CR ion?) Pc.1 ion cells. We further postulate that each compartment comprises at least two phases; one in which genetic programming occurs and the other in which induction of cells by an exgernal signal allows their rapid transition to the next compartment in sequence. Our main emphasis will be to study the conditions which allow a B cell resident in any of the four precursor compartments to ahcieve the inducible ("poised") state. Many cells are refractory to the inductive stimulus and presumably progress to the inducible state under appropriate environmental conditions. We plan to isolate such refractory cells from normal adult mice, from fetal tissues in which sequence of B cells is not yet complete, or from strains with deviations in B cell development. We will investigate the influence of stromal tissues from several lymphoid organs (bone marrow, spleen, thymus, fetal liver) on the generation of inducible cells from refractory populations. Ultimately we hope to drive cells in vitro through two adjacent compartments, e.g., from the Ig- to the Ig ion Ia- compartments and subsequently to Ig ion Ia ion cells. The requirement of this process for cell division (DNA synthesis, mitosis, cytokinesis), RNA and protein synthesis will be investigated by use of inhibitors. The immunological capacity of some of the later B cell compartments will be determined in vitro with the aim of identifying the immediate precursor of the antibody synthesizing cell (PFC).